PGE2 诱导的支气管扩张在 III 组肺动脉高压中受损。
- 作者列表："Ozen G","Benyahia C","Mani S","Boukais K","Silverstein AM","Bayles R","Nelsen AC","Castier Y","Danel C","Mal H","Clapp LH","Longrois D","Norel X
BACKGROUND AND PURPOSE:In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE2 and PGI2 induce potent relaxation of human bronchi from non-PH (control) patients via EP4 and IP receptors, respectively. However, the effects of PGE2 /PGI2 and their mimetics on human bronchi from PH patients are unknown. Here, we have compared relaxant effects of several PGI2 -mimetics approved for treating PH Group I with several PGE2 -mimetics, in bronchial preparations derived from PH Group III and control patients. EXPERIMENTAL APPROACH:Relaxation of bronchial muscle was assessed in samples isolated from control and PH Group III patients. Expression of prostanoid receptors was analysed by western blot and real-time PCR, and endogenous PGE2 , PGI2 , and cAMP levels were determined by ELISA. KEY RESULTS:Maximal relaxations induced by different EP4 receptor agonists (PGE2 , L-902688, and ONO-AE1-329) were decreased in human bronchi from PH patients, compared with controls. However, maximal relaxations produced by PGI2 -mimetics (iloprost, treprostinil, and beraprost) were similar for both groups of patients. Both EP4 and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH patients. cAMP levels significantly correlated with PGI2 but not with PGE2 levels. CONCLUSION AND IMPLICATIONS:The PGI2 -mimetics retained maximal bronchodilation in PH Group III patients, whereas bronchodilation induced by EP4 receptor agonists was decreased. Restoration of EP4 receptor expression in airways of PH Group III patients with respiratory diseases could bring additional therapeutic benefit.
背景和目的: 在肺疾病和/或缺氧相关的肺动脉高压 (PH) 患者 (ⅲ 组) 中，肺血管张力降低和组织缺氧对治疗有益。PGE2 和 PGI2 分别通过 EP4 和 IP 受体诱导非 PH (对照) 患者的人支气管强效舒张。然而，PGE2/PGI2 及其模拟物对 PH 患者人支气管的影响尚不清楚。在此，我们比较了批准用于治疗 PH 组 I 的几种 PGI2 模拟物与几种 PGE2 模拟物在来自 PH 组 III 和对照患者的支气管制剂中的松弛作用。 实验方法: 在从对照组和 PH 组 III 患者分离的样本中评估支气管肌肉的松弛。Western blot 和实时PCR 分析前列腺素受体的表达，ELISA 测定内源性 PGE2 、 PGI2 和 cAMP 水平。 关键结果: 与对照组相比，不同 EP4 受体激动剂 (PGE2 、 L-902688 和 ONO-AE1-329) 诱导的 PH 患者人支气管最大松弛减少。然而，两组患者 PGI2 模拟药 (伊洛前列素、曲前列素和贝前列素) 产生的最大松弛作用相似。PH 患者人支气管 EP4 和 IP 受体蛋白和 mRNA 表达均显著降低。CAMP 水平与 PGI2 显著相关，但与 PGE2 水平无关。 结论和意义: PGI2 模拟物保留了 PH 组 III 患者的最大支气管扩张，而 EP4 受体激动剂诱导的支气管扩张减少。恢复 EP4 受体在 PH 组 III 呼吸系统疾病患者气道中的表达可带来额外的治疗益处。
METHODS:Background Dye localization is a useful method for the resection of unidentifiable small pulmonary lesions. This study compares the transbronchial route with augmented fluoroscopic bronchoscopy (AFB) and conventional transthoracic CT-guided methods for preoperative dye localization in thoracoscopic surgery. Methods Between April 2015 and March 2019, a total of 231 patients with small pulmonary lesions who received preoperative dye localization via AFB or percutaneous CT-guided technique were enrolled in the study. A propensity-matched analysis, incorporating preoperative variables, was used to compare localization and surgical outcomes between the two groups. Results After matching, a total of 90 patients in the AFB group ( N = 30) and CT-guided group ( N = 60) were selected for analysis. No significant difference was noted in the demographic data between both the groups. Dye localization was successfully performed in 29 patients (96.7%) and 57 patients (95%) with AFB and CT-guided method, respectively. The localization duration (24.1 ± 8.3 vs. 21.4 ± 12.5 min, p = 0.297) and equivalent dose of radiation exposure (3.1 ± 1.5 vs. 2.5 ± 2.0 mSv, p = 0.130) were comparable in both the groups. No major procedure-related complications occurred in either group; however, a higher rate of pneumothorax (0 vs. 16.7%, p = 0.029) and focal intrapulmonary hemorrhage (3.3 vs. 26.7%, p = 0.008) was noted in the CT-guided group. Conclusion AFB dye marking is an effective alternative for the preoperative localization of small pulmonary lesions, with a lower risk of procedure-related complications than the conventional CT-guided method.
METHODS:Background The use of artificial intelligence, including machine learning, is increasing in medicine. Use of machine learning is rising in the prediction of patient outcomes. Machine learning may also be able to enhance and augment anesthesia clinical procedures such as airway management. In this study, we sought to develop a machine learning algorithm that could classify vocal cords and tracheal airway anatomy real-time during video laryngoscopy or bronchoscopy as well as compare the performance of three novel convolutional networks for detecting vocal cords and tracheal rings. Methods Following institutional approval, a clinical dataset of 775 video laryngoscopy and bronchoscopy videos was used. The dataset was divided into two categories for use for training and testing. We used three convolutional neural networks (CNNs): ResNet, Inception and MobileNet. Backpropagation and a mean squared error loss function were used to assess accuracy as well as minimize bias and variance. Following training, we assessed transferability using the generalization error of the CNN, sensitivity and specificity, average confidence error, outliers, overall confidence percentage, and frames per second for live video feeds. After the training was complete, 22 models using 0 to 25,000 steps were generated and compared. Results The overall confidence of classification for the vocal cords and tracheal rings for ResNet, Inception and MobileNet CNNs were as follows: 0.84, 0.78, and 0.64 for vocal cords, respectively, and 0.69, 0.72, 0.54 for tracheal rings, respectively. Transfer learning following additional training resulted in improved accuracy of ResNet and Inception for identifying the vocal cords (with a confidence of 0.96 and 0.93 respectively). The two best performing CNNs, ResNet and Inception, achieved a specificity of 0.985 and 0.971, respectively, and a sensitivity of 0.865 and 0.892, respectively. Inception was able to process the live video feeds at 10 FPS while ResNet processed at 5 FPS. Both were able to pass a feasibility test of identifying vocal cords and tracheal rings in a video feed. Conclusions We report the development and evaluation of a CNN that can identify and classify airway anatomy in real time. This neural network demonstrates high performance. The availability of artificial intelligence may improve airway management and bronchoscopy by helping to identify key anatomy real time. Thus, potentially improving performance and outcomes during these procedures. Further, this technology may theoretically be extended to the settings of airway pathology or airway management in the hands of experienced providers. The researchers in this study are exploring the performance of this neural network in clinical trials.
METHODS:BACKGROUND:The optimal mode of delivering topical anesthesia during flexible bronchoscopy remains unknown. This article compares the efficacy and safety of nebulized lignocaine, lignocaine oropharyngeal spray, or their combination. METHODS:Consecutive subjects were randomized 1:1:1 to receive nebulized lignocaine (2.5 mL of 4% solution, group A), oropharyngeal spray (10 actuations of 10% lignocaine, group B), or nebulization (2.5 mL, 4% lignocaine) and two actuations of 10% lignocaine spray (group C). The primary outcome was the subject-rated severity of cough according to a visual analog scale. The secondary outcomes included bronchoscopist-rated severity of cough and overall procedural satisfaction on a visual analog scale, total lignocaine dose, subject's willingness to undergo a repeat procedure, adverse reactions to lignocaine, and others. RESULTS:A total of 1,050 subjects (median age, 51 years; 64.8% men) were included. The median (interquartile range) score for subject-rated cough severity was significantly lower in group B compared to group C or group A (4 [1-10] vs 11 [4-24] vs 13 [5-30], respectively; P < .001). The bronchoscopist-rated severity of cough was also the least (P < .001), and the overall satisfaction was highest in group B (P < .001). The cumulative lignocaine dose administered was the least in group B (P < .001). A significantly higher proportion of subjects (P < .001) were willing to undergo a repeat bronchoscopy in group B (73.7%) than in groups A (49.1%) and C (59.4%). No lignocaine-related adverse events were observed. CONCLUSIONS:Ten actuations of 10% lignocaine oropharyngeal spray were superior to nebulized lignocaine or their combination for topical anesthesia during diagnostic flexible bronchoscopy. TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT03109392; URL: www.clinicaltrials.gov.